Transcranial ultrasound localization microscopy in moyamoya patients using a clinical ultrasound system

Background: Deep brain structures are supplied by perforating arteries, which are too thin to be observed with non-invasive and widely available clinical imaging methods. In moyamoya disease, main arteries in the base of the brain progressively narrow, and perforating arteries grow densely and tortuously to compensate the lack of blood supply in deep brain structures. Purpose: The aim of this study is to evaluate the efficacy of transcranial ultrasound localization microscopy (ULM) in visualizing perforating arteries, utilizing a standard low-frame-rate ultrasound clinical scanner and contrast sequences commonly employed in hospital settings. Methods: This prospective single-center study included ischemic stroke patients not related to the study of perforating arteries, and moyamoya disease patients. Contrast-enhanced ultrasound sequences (CEUS) were performed by an experienced neurologist and the images acquired were used to perform post-processing ULM. ULM density maps were compared with conventional 3T TOF MRI and color Doppler imaging in both groups. Results: We included a group of 15 control patients and another group of 9 moyamoya patients between March 2023 and March 2024. The patients had an average age of 45 ± 14 years (65% male). Perforating arteries were captured on all subjects, with a mean diameter of 0.8 ± 0.3 mm in control patients, while it was not possible with TOF MRI or color Doppler (P < 0.05). Moreover, ULM enabled to highlight differences between healthy subjects and those with moyamoya disease through track mean distance (P = 0.05). Conclusions: Using a low-frame-rate ultrasound scanner, CEUS and accessible post-processing tools, we demonstrate that transcranial ULM can facilitate the visualization and characterization of perforating arteries, even in cases where they were previously undetectable using standard non-invasive imaging techniques. We speculate that with the advent of high-frame-rate 3D ULM, this technique may find widespread utility in hospitals.